FAPi Radioligand OpeN-Label, Phase 1 Study to Evaluate Safety, Tolerability and DosImetry of [Lu-177]-PNT6555; A Dose Escalation Study for TReatment of Patients With Select Solid Tumors (FRONTIER)

This Phase 1 study will evaluate the safety and tolerability of [Ga-68]-PNT6555 and [Lu-177]-PNT6555 in subjects with select solid tumors that have FAP over-expression, in order to determine a recommended Phase 2 dose.

Study Overview

• Status: Terminated
• Conditions: Soft Tissue Sarcoma; Colorectal Cancer; Esophageal Cancer; Cholangiocarcinoma; Head and Neck Squamous Cell Carcinoma; Pancreatic Ductal Adenocarcinoma; Melanoma (Skin)
• Intervention / Treatment: Drug: [Ga-68]-PNT6555; Drug: [Lu-177]-PNT6555

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • University Health Network - Princess Margaret Cancer Centre
  • Quebec
    • Montréal, Quebec, Canada, H3T 1E2
      • Jewish General Hospital
    • Montréal, Quebec, Canada, H2X 3E4
      • CHUM - Centre Hospitalier de l'Universite de Montreal
• United States
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Adult (>18 years) male and female patients
2. Females of childbearing potential and males and their female partner(s) of childbearing potential must use two acceptable forms of contraception, one being a barrier method, during the study and also for 31 weeks (females) or 18 weeks (males) after last study drug administration.
3. Patients are willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations
4. The patient has read, understood, and signed the written informed consent form(s)

5. Advanced or metastatic solid tumor that is refractory to standard treatment, for which no standard treatment is available, or it is contraindicated, or the patient refuses standard therapy:

   • Adenocarcinoma of the Pancreas
   • High grade Soft Tissue Sarcoma (excluding Chordoma)
   • Esophageal Cancer (Squamous Cell Carcinoma or Adenocarcinoma, excluding Gastroesophageal Junction Cancer at US sites only)
   • Colorectal Cancer
   • Melanoma Skin Cancer
   • Head and Neck Squamous Cell Carcinoma (oral cavity, oropharynx, hypopharynx, nasopharynx, and larynx) (only at Canadian sites)
   • Cholangiocarcinoma (only at Canadian sites)

6. Laboratory values at initial screening and also within three days prior to dosing of [Lu-177]-PNT6555:

   1. Platelets greater than 120,000/ mm^3 at dosing. Transfusions allowed, but not for first dose
   2. Neutrophils greater than 1500cells/mm^3

   3. Hemoglobin:

      • Greater than 8.0 g/dL (only in Canada)
      • Greater than 8.5 g/dL (only in US)

   4. Liver Chemistries:

      • ALT and AST < 2.5 x ULN or < 5 x ULN for patients with liver metastases
      • Bilirubin < 2 mg/dL (<34.2 µmol/L); patients with Gilbert's syndrome are permitted if bilirubin is < 3 mg/dL (< 51.3 µmol/L) (only in Canada).
      • Total Bilirubin ≤ 1.5 x upper limit of normal (ULN); Total bilirubin ≤ 3 ULN is acceptable if a patient has Gilbert's provided that direct bilirubin ≤ 1.5 ULN (only in US)
   5. Normal PT(secs) and aPTT(sec); normal INR (ratio). Patients taking anticoagulants must be in therapeutic range
7. Glomerular filtration rate defined as creatinine clearance >60 ml/min/1.73 m2 based on Cockcroft-Gault formula
8. Life expectancy of at least 6 months per investigator judgement
9. Eastern Cooperative Oncology Group (ECOG) 0 to 1
10. Patients must have previously received treatment for their underlying disease and have no potentially curative options available
11. Positive [Ga-68]-PNT6555 PET/CT scan, defined as at least 50% of lesions with an SUVmax of 1.5 times or greater the SUVmean of the liver

Exclusion criteria

1. Patient has metastatic brain disease
2. Women who are pregnant, lactating, or planning to attempt to become pregnant during the study or within 31 weeks after last administration of study drug
3. Males with female partners who are pregnant, lactating or planning to attempt to become pregnant during this study or within 18 weeks after last administration of study drug
4. Subject has received prior hemi- or total- body radiation
5. Subject has received whole brain radiation
6. History of any grade 4 myelosuppression, or grade 3 myelosuppression requiring more than 6 weeks recovery
7. History of any kidney dysfunction (e.g., acute kidney failure, acute tubular necrosis (ATN)) for any reason (only in US)
8. Secondary malignancy that may interfere with the safety assessments of this study

9. Patient has any concurrent severe and/or uncontrolled medical conditions that could increase the patient's risk for toxicity while on the study or that could confound discrimination between disease- and study treatment-related toxicities

   a. Or the patient has persistent NCI-CTCAE version 5.0 Grade ≥ 2 toxicity due to prior cancer therapy. Permitted exceptions include Grade 2 neuropathy, alopecia, endocrinopathy with replacement therapy, and anemia (only in US)

10. Patient has received any other investigational agents within 4 weeks of starting the study treatment

11. Patient has received systemic anti-cancer therapy:

    1. Within 4 weeks or 5 half-lives, whichever is shorter of starting the study treatment; hormone maintenance therapy may be permitted with approval by the medical monitor if the patient is on a stable dose (preferred duration of a stable dose will be 4 weeks) (only in Canada)
    2. Patient has received systemic anti-cancer therapy within 4 weeks of starting the study treatment; hormone maintenance therapy may be permitted with approval by the medical monitor if the patient is on a stable dose (preferred duration of a stable dose will be 4 weeks) (only in US)
12. Patient has undergone surgery within 4 weeks of starting the study treatment; exceptions are permitted with approval by Medical Monitor
13. Previous radioligand therapy
14. Previous Adoptive T-Cell Therapy (e.g. CAR-T therapy, TCR therapy, etc.)
15. Prolonged QT, defined as QTc > 470 ms regardless of sex (only in US)
16. In patients who have received prior EBRT, each case should be reviewed by the site Investigators to determine appropriateness of eligibility given potential increased risk for radiation toxicities. In patients who have received a prior course of radiation therapy adjacent to either kidney, the mean kidney dose from EBRT must be available to inform potential risk, otherwise the patient will be ineligible. Patients who have previously exceeded dose limits for critical organs from prior EBRT are ineligible (only in US)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose escalation; Up to 30 patients with FAP-avid solid tumors.	Drug: [Ga-68]-PNT6555; [Ga-68]-PNT6555 IV administered as imaging agent for PET/CT; Drug: [Lu-177]-PNT6555; Patients with FAP-avid disease as determined by the [Ga-68]-PNT6555 screening PET/CT will receive [Lu-177]-PNT6555 at a fixed dose level for up to 6 doses at an interval of 6 weeks between each dose.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment emergent adverse events	Occurrence of Treatment emergent adverse events as per CTCAE v5.0	From first dose of study drug through end of treatment (~24 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events for [Ga-68]-PNT6555	Occurrence of adverse events for [Ga-68]-PNT6555 as per CTCAE v5.0	From first dose of imaging study drug through 7 days post dose
Biodistribution and radiation dosimetry of [Lu-177]-PNT6555 to normal organs.	Absorbed dose estimates (Gy) in normal organs for [Lu-177]-PNT6555	From first dose of study drug through end of treatment (~24 weeks)
Biodistribution and radiation dosimetry of [Ga-68]-PNT6555 to normal organs.	Absorbed dose estimates (Gy) in normal organs for [Ga-68]-PNT6555	From first dose of imaging study drug through 7 days post dose
Detection of [Ga-68]-PNT6555 in tumor lesions	Anatomic distribution of [Ga-68]-PNT6555	From first dose of imaging study drug through 7 days post dose
Uptake of [Ga-68]-PNT6555 in tumor lesions	Maximum and average standardized uptake values of [Ga-68]-PNT6555 in tumor lesions	From first dose of imaging study drug through 7 days post dose

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Preliminary efficacy of [Lu-177]-PNT6555 based on tumor response.	Objective response rate (ORR) based on RECIST 1.1	From first dose of study drug until disease progression (up to approximately 3 years)
Preliminary efficacy of [Lu-177]-PNT6555 based on change in biomarkers.	CA 19-9, CEA	From first dose of study drug through end of treatment (~24 weeks)
Radiation dosimetry of [Lu-177]-PNT6555 to tumor lesions.	Absorbed dose estimates (Gy) in tumor lesions for [Lu-177]-PNT6555	From first dose of study drug through end of treatment (~24 weeks)
Tumor immune response to administration of [Lu-177]-PNT6555.	Circulating immune cell changes	From first dose of study drug through end of treatment (~24 weeks)
Uptake of the [Ga-68]-PNT6555 imaging agent and optimal scanning specifications for future studies	[Ga-68]-PNT6555 SUV at 0 - 60, 60, 90, and 120 min of tumor lesions and normal organs	From first dose of imaging study drug through two hours post dose

Collaborators and Investigators

• Sponsor: POINT Biopharma, a wholly owned subsidiary of Eli Lilly and Company
• Investigators: Study Director: Jessica Jensen, Eli Lilly and Company

Study record dates

Study Major Dates

• Study Start (Actual): July 13, 2022
• Primary Completion (Actual): November 10, 2023
• Study Completion (Actual): October 2, 2024

Study Registration Dates

• First Submitted: June 8, 2022
• First Submitted That Met QC Criteria: June 22, 2022
• First Posted (Actual): June 27, 2022

Study Record Updates

• Last Update Posted (Estimated): June 25, 2025
• Last Update Submitted That Met QC Criteria: June 19, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: Lu-177; Melanoma; HNSCC; Cholangiocarcinoma; Esophageal cancer; CRC; PDAC; STS; radioligand therapy; FAP; fibroblast activation protein; FRONTIER; PNT6555; 177Lu-FAP; 68Ga-FAP; FAPi; GA-68
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Head and Neck Neoplasms; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Esophageal Diseases; Skin Diseases; Carcinoma; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Neoplasms, Connective and Soft Tissue; Nevi and Melanomas; Skin Neoplasms; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Esophageal Neoplasms; Cholangiocarcinoma; Melanoma; Sarcoma
• Other Study ID Numbers: PNT6555-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No